Many patients with chronic illnesses such as AIDS, tuberculosis or autoimmune diseases suffer from a mysterious additional disease: cachexia. It affects approximately 80 percent of cancer patients. This highly complex and poorly understood syndrome results in uncontrolled weight loss and muscular dystrophy; it has a significant impact on the likelihood of premature death. Despite the enormous need for clinical care, the standards for diagnosing and treating patients with cachexia continue to be insufficient, and the options for effective treatment are limited.
In cooperation with researchers from the University of Graz, the Medical University of Vienna as well as partners from Germany, Switzerland and the US, a research group headed by Andreas Bergthaler from the Austrian Academy of Sciences’ Centre for Molecular Medicine (CeMM) has now analysed a mechanism which explains how chronic viral infections can lead to cachexia. The results of the study have been published in the most recent edition of Nature Immunology.
Restructured adipose tissue
Researchers were able to identify key molecular players that lead to cachexia in people suffering from chronic infections. Their research shows that the viral infections caused a drastic reorganisation of the architecture of adipose tissue. This was associated with the activation of lipolysis, a wave of molecular processes which cause the body to use up its fat reserves. According to Hatoon Baazim, a doctoral student at CeMM and the first author of the study, ‘What was surprising was that none of the inflammatory mediators known to cause cachexia in cancer patients played a role in our study’.
T-killer cells influence the development of virally induced cachexia
During the course of their analyses of other potential mechanisms, the researchers concluded that one particular type of cell in the body’s immune system was responsible for causing cachexia: CD8-T-cells. Also known as T-killer cells, these immune cells normally recognise when cells have been infected with a virus or have become cancerous; they then destroy these cells. The study was able to show for the first time that CD8-T-cells played a fundamental role in triggering cachexia in infections. Additional signals from the antiviral cytokine known as Interferon type I, a neurotransmitter produced by the body’s immune system, as well as recognition of the virus by CD8-T-cells play an important role in this mechanism. ‘Virally induced cachexia differs from carcinogenically induced cachexia in two ways: its reversibility on the one hand and, on the other hand, the fact that it is not triggered by the cytokines typically associated with infections. Rather, it is the body’s immune response to the virus, the T cells, which induce a change in adipose tissue leading to a complete depletion of fat reserves. If the immune response is inhibited during the viral infection, this could protect patients from cachexia’, explains Martina Schweiger from the Institute of Molecular Biosciences at the University of Graz. She and Rudolf Zechner were actively involved in the publication.
Innovative therapeutic strategies
This study provides the international research community with a valuable tool for additional research on the molecular mechanisms of cachexia. It can contribute to a better understanding of infections such as AIDS, tuberculosis, malaria and other parasitic diseases which cause cachexia. This new knowledge from basic research could lead to the development of innovative therapeutic strategies to combat cachexia and the life-threatening chronic illnesses associated with it. The study was sponsored by the European Research Council (ERC), the Austrian Academy of Sciences, the Austrian Science Fund (FWF), the German Research Foundation (DFG) and the US National Institutes of Health.
Publication: Baazim, Schweiger et.al.: CD8+ T cells induce cachexia during chronic viral infection, Nature Immunology (20.5.2019). DOI: DOI: 10.1038 / s41590-019-0397-y
